Combinations of closely situated cis-acting elements determine tissue-specific patterns and anterior extent of early Hoxc8 expression

We have used a transgene mutation approach to study how expression domains of Hoxc8 are established during mouse embryogenesis. A cis-regulatory region located 3 kb upstream from the Hoxc8 translational start site directs the early phase of expression. Four elements, termed A, B, C, and D, were previously shown to direct expression to the neural tube. Here we report that a fifth element, E, located immediately downstream of D directs expression to mesoderm in combination with the other four elements. These elements are interdependent and partially redundant. Different combinations of elements determine expression in different posterior regions of the embryo. Neural tube expression is determined minimally by ABC, ABD, or ACD; somite expression by ACDE; and lateral plate mesoderm expression by DE. Neural tube and lateral plate mesoderm enhancers can be separated, but independent somite expression has not been achieved. Furthermore, mutations within these elements result in posteriorization of the reporter gene expression. Thus, the anterior extent of expression is determined by the combined action of these elements. We propose that the early phase of Hoxc8 expression is directed by two separate mechanisms: one that determines tissue specificity and another that determines anterior extent of expression.     

Meniscal repair using the inside-to-outside technique

The frequent occurrence of degenerative joint disease following complete or partial meniscectomy is well recognized. Meniscal repair has been shown to lead to a lower prevalence of degenerative changes in the knee. Arthroscopically assisted inside-to-outside meniscal repair is a safe, reproducible technique for for salvaging the torn meniscus.     

Data quality review program: the Society of Thoracic Surgeons Adult Cardiac National Database

In summary, the National Database Committee's Audit and Validation Subcommittee is working to maximize the data completeness and quality of the STS National Database. Toward this end, we welcome your suggestions for improvement.     

Large-scale screening for factor V Leiden mutation in a north-eastern German population

A 37-year-old man was referred with thoracic pain after a deceleration trauma. He also had a cerebral contusion and a wrist fracture. There were no sings of hypovolemic shock. Computerized tomography (CT) of the chest and transoesophageal echocardiography (TEE) demonstrated a type B aortic dissection originating just distal to the left subclavian artery. There was a patent false lumen without rupture or distal ischaemia. Conservative treatment was given. A paralytic ileus developed and abdominal complaints persisted for several months. Angiography showed normal patency of mesenteric vessels. On follow-up, 3 years after the accident a slight aortic dilation was found on CT thorax without development of a post-dissection aneurysm. Blunt thoracic injury to the aorta usually gives rise to aortic rupture in the region of the isthmus, which can be complete or partial. In the latter case a false aneurysm may develop. An intimal tear after blunt trauma leading to type B aortic dissection rarely occurs. General principles regarding treatment of type B dissection also apply to this particular condition.     

Tendons attached to prostheses by tendon-bone block fixation: an experimental study in dogs

To develop a method of tendon attachment to a metallic endoprosthesis, we evaluated fixation strength, clinical function of the tendon, and morphological changes in an experimental model. The canine supraspinatus tendon was removed from the greater tubercle of the humerus and attached to a titanium prosthesis. In 12 animals, the bone block underlying the tendon insertion was preserved and attached in one limb; the soft part of the tendon was attached directly to the prosthesis in the contralateral limb. Fixation strength was evaluated after 16 weeks of in vivo implantation (12 specimens) and compared with the in vitro fixation strength (12 specimens) and with intact normal controls (six specimens from cadavera). Function of the tendon in vivo was evaluated by force-plate analysis (at 3-week intervals). All specimens were evaluated histologically. Sixteen weeks after surgery, the tendon-bone block attachment was significantly stronger (mean, 16%) than the direct tendon attachment and not significantly different from the normal control, and the direct tendon attachment was significantly weaker (mean, 68%) than the normal control. There was significantly more weight-bearing on the limbs with a tendon-bone block attachment than on the limbs with a direct tendon attachment at both 3 and 6 weeks postoperatively. Both front legs showed increased weight-bearing with time, but the differences were not statistically significant. Anchorage by tissue ingrowth to the titanium prosthesis was found consistently--there was bone ingrowth in the tendon-bone block attachments and fibrous tissue ingrowth in the direct tendon attachments. When a bone block was preserved, the strength and stiffness were comparable with those of a normal tendon insertion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Why quality of life measures should be used in the treatment of patients with respiratory illness

Treatment of airways disease is directed towards improving patients' health and well-being. Measurements of airways function do not reflect all the disease activity present in the airways that may affect the patient. Spirometry correlates poorly with health. Physicians appear to estimate their patients' health using criteria different from the patients themselves. Quality of life questionnaires provide a method of quantifying the effect of disease on patients' lives. They can summarize a number of aspects of the disease and provide an overall estimate of the effect of disease and benefits due to therapy. They have the potential to identify a threshold response to treatment that may be considered "worthwhile", and allow comparison between therapies with respect to the health gain that each provides.     

Novel technique and instrumentation for laparoscopic application of hemostatic clips

A novel device for applying hemostatic clips in laparoscopic surgery incorporates a distal hook into a multiple-firing titanium clip applier. The hook may be used for blunt dissection of tissue, and to displace and control ducts and vessels during clip application. A single instrument may be used to achieve hemostasis in areas that are difficult to reach, and past pointing problems encountered with straight on clip appliers are alleviated. Comparative testing of the holding force of the curved clips used with this device versus the straight clips used in conventional multiple-clip appliers demonstrated a higher mean pull-off force of 0.473 lbs versus 0.33 lbs. Clinical application of the device in laparoscopic procedures including cholecystectomy, vaginal hysterectomy, Nissen fundoplication, vagotomy, varicocelectomy, and lymphadenectomy show the utility of the hook clip applier.     

Fear of humans in Japanese quail selected for low or high adrenocortical response

Behavioral reactions to a nearby human were recorded in male Japanese quail of two lines selected for reduced (LS; low stress) or exaggerated (HS; high stress) plasma corticosterone (B) response to brief mechanical immobilization. Their adrenocortical responses to one of three treatments were then examined. These were: no human disturbance (undisturbed controls, CON), capture and return to the home cage before recapture and bleeding after 5 min (CR), or capture and manual restraint for 5 min before blood sampling (CREST). Quail of the HS line showed more fear-related behavior (crouching, escape) and avoidance of the experimenter than did their LS counterparts. Plasma B concentrations were markedly elevated following each capture treatment (CREST > CR) and the response appeared to be more pronounced in quail of the HS than the LS line. These findings indicate that HS quail perceived human contact to be more aversive than did those of the LS line. Avoidance scores and the adrenocortical responses to capture were positively correlated within individual birds. Therefore, simple behavioral tests of fear may have predictive value concerning physiological responsiveness to stressful stimulation.     

Outcome of orthotopic liver transplantation in patients with haemophilia

As part of environmental toxicology, it is important to assess both the carcinogenic potential of xenobiotics and their mode of action on target cells. Since dysregulation of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, is considered as an early and essential component in the process of multistage carcinogenesis, we have studied the mode of ODC induction in Syrian-hamster-embryo(SHE) cells stage-exposed to carcinogens and to non-carcinogens. One-stage (5 hr) treatment of SHE cells with 50 microM clofibrate (CLF), a non-genotoxic carcinogen, or with 0.4 microM benzo(a)pyrene (BaP), a genotoxic carcinogen, slightly decreased basal ODC activity. Using the 2-stage exposure, 1 hr to carcinogen, then replacement by TPA for 5 hr, the ODC activity was higher than that obtained with TPA alone. This ODC superinduction was not observed when SHE cells were similarly pre-treated with non-carcinogenic compounds. Several environmental chemicals, pesticides, solvents, oxidizers and drugs were investigated with this SHE cell model. With one-stage exposure, some xenobiotics decreased basal ODC activity, while for others ODC changes were not noticeable. With 2-stage exposure (chemical followed by TPA), all carcinogens amplified the TPA-inducing effect, resulting in ODC superinduction. Comparative studies of the action of carcinogens and of non-carcinogens, using 2-stage exposure protocols, clearly show a close relationship between ODC induction rate and morphological transformation frequency.